Göran Steg

Chapter 83 Neural transplantation in Parkinson's disease: the Swedish experience

Publisher Summary This chapter discusses the neural transplantation in Parkinsons disease (PD). The fetal nigral implants have provided a modest improvement in motor function in PD patients. This is consistent with the presence of small surviving grafts indicated by positron emission tomography (PET). Despite the lack of a therapeutically significant improvement in these patients, results together with the solid animal experimental data obtained with DA neuron grafting both in rodents and in non-human primates provide a strong rationale to pursue this approach. However, widespread clinical trials with neural transplantation in PD are probably not warranted at this time. From the observations made on the 2 patients reported in the chapter, the following conclusions are drawn: (1) ventral mesencephalic tissue obtained from routine elective abortions can be implanted into the brains of immunosuppressed PD patients without major complications; (2) no major graft-induced improvement of therapeutic value to the patients has been observed; (3) neurophysiological methods and the clinical test battery have detected significant but small post-operative improvements that could indicate a graft effect; and (4) PET provides an evidence of a slight increase of 18 F-dopa uptake in the transplanted striatum, suggesting that small grafts have survived.

Reflexive Limb Selection and Control of Reach Direction to Moving Targets in Cats, Monkeys, and Humans

When we reach for an object, we have to decide which arm to use and the direction in which to move. According to the established view, this is voluntarily controlled and programmed in advance in time-consuming and elaborate computations. Here, we systematically tested the motor strategy used by cats, monkeys, and humans when catching an object moving at high velocity to the left or right. In all species, targets moving to the right selectively initiated movement of the right forelimb and vice versa for targets moving to the left. Movements were from the start directed toward a prospective target position. In humans, the earliest onset of electromyographic activity from start of motion of the target ranged from 90 to 110 ms in different subjects. This indicates that the selection of the arm and specification of movement direction did not result from the subjects voluntary decision, but were determined in a reflex-like manner by the parameters of the target motion. As a whole the data suggest that control of goal-directed arm movement relies largely on an innate neuronal network that, when activated by the visual signal from the target, automatically guides the arm throughout the entire movement toward the target. In the view of the present data, parametric programming of reaching in advance seems to be superfluous.

Motor Functions of the Striatum

Publisher Summary This chapter describes motor functions of the striatum. Parkinsons disease presents at least three major symptoms of disturbed motor control, namely hypokinesia, augmented muscle tone, and a characteristic alternating tremor of the limbs and the trunk. In Parkinsons disease, it is often possible to reverse the hypokinetic–hypertonic syndrome into a hyperkinetic–hypotonic counterpart by giving an overdose of levodopa or dopamine agonists such as apomorphine. With levodopa, it is possible to modulate these motor functions between the two extremes by dose adjustments. Parkinsonian tremor is thought to be a centrally induced phenomenon relying upon the integrity of certain loops in the brain including the efferent pathways of the striatum and the cortex cerebri as it can be relieved after lesions in the ventrolateral thalamic nuclei and as it is absent after removal of the motor cortex in man. Clinical data indicate that the augmented muscle tone in Parkinsons disease depends on striatal dysfunction and that there is no primary malfunction at spinal or peripheral levels.

A mechanographic method for measurement of locomotor activity in rats. Effects of dopaminergic drugs and electric stimulation of the brainstem

A simple treadmill arrangement has been developed to quantify the quadruped or hindleg locomotor activity in rats. The method provides information on the accumulated distance passed by the rat in the treadmill but also on the temporal distribution of locomotion and the stepping cycle. It can be used with intact rats but also during stereotaxically guided electric stimulation of the brain. The accumulated locomotion produced by apomorphine showed a partly linear relation to the dose and the results were comparable to those found with other methods. The locomotor effect of brainstem stimulation was enhanced by apomorphine. This method combines the advantages of several other methods and is well suited as a tool for the analysis of nervous regulation of locomotor activity.

Manual transport in Parkinson's disease

We analyze hand dexterity in Parkinsons disease patients (PD) and control subjects using a natural manual transport task (moving an object from one place to another). Eight PD patients and 10 control subjects carried out the task repeatedly at maximum speed both in off and on medicated status. The movement parameters and the grip and load forces were recorded. Using the force and velocity signals, 10 subsequent phases of the transport movement were defined and their durations were measured. The difference between the control group and the test group in off and on was established statistically using non‐parametric methods. There was slowed reaching and a striking disturbance of establishing the precision grip in PD. The transport capabilities were impaired differentially. Although acceleration and reaching sufficient height of the lift were disturbed in PD subjects, transport of the object toward the target position was almost normal. A partial disturbance was observed when cancelling the grip. Dopaminergic medication improved only specific hand skills, especially establishment of the precision grip and one of the four transport phases. A long movement path was more sensitive for movement disturbance in Parkinsons disease than a short one.© 2003 Movement Disorder Society

Motor function in 90-year olds measured by optoelectronic kinesiology and activities of daily living

Computer-assisted optoelectronic movement analysis using a Posturo-Locomotor-Manual (PLM) test, and assessment with an ADL (Activities of Daily Living) scale were performed in 36 ( 18 women and 18 men) 90-year-old subjects as part of a larger study. In the PLM test, the subjects were asked to pick up an object placed on the floor, and carry it to a shelf at the height of their chin and at a distance of 150 cm from the starting position. In the ADL assessment, the subjects were classified as ADL-dependent or independent in each of 4 instrumental (cleaning, shopping, transport and cooking) and 5 personal activities (bathing, dressing, going to the toilet, transfer and feeding). ADL independence was defined as being able to perform ADL activities without assistance from another person. In this study, ADL-dependent subjects performed the PLM test considerably more slowly than the ADL-independent group. A correlation was found in females between poorer ADL performance and slower and less co-ordinated PLM test results. Particularly, the Postural and Locomotor phases representing lower limb mobility correlated to the ADL steps. In males, no such correlation was found, indicating that factors other than mobility were important for ADL performance in this group, e.g., cooking skills. The relationships between the PLM test and the ADL assessment estimating practical motor function could be an indication that the PLM test is not only a strict laboratory method, but also measures components of everyday motor activities. Combined use of optoelectronic measurements and ADL scales will improve measurements of motor performance in elderly persons. (Aging Clin. Exp. Res. 6: 444-450, 1994)

Dissolution of Motor Program Coordination in Parkinson’s Disease

One purpose of this paper is to show that the concepts of locomotor physiology as they have been expressed in this symposium are useful for the analysis of motor disorders of basal ganglia diseases such as Parkinson’s disease.

A mechanographic method for measurement of muscle tone in the conscious rat. The calf muscle stretch response in reserpine-induced rigidity

A simple mechanographic method for the measurement of muscle tone in awake rats is presented. It utilizes principles corresponding to those in clinical assessment of tone and it has been applied to an animal model of Parkinsons disease: the reserpine-treated rat. The rat was restrained by a plastic cylinder and by metal cuffs at the ankles. The hind feet were repeatedly dorsiflexed by an electromechanical manipulator and the resulting calf muscle tension was indirectly measured with a strain-gauge system. The relative contributions to the stretch response from the different muscle groups acting on the ankle joint in the awake and untreated rat and during reserpine-induced rigidity are described. Very little active tension was found in the untreated rat. After treatment with reserpine, continuous activation of the muscle was found in EMG recordings and there was a sharp increase in the tension recorded during stretch. The static response to the increased isometric stretch was augmented. An additional, tonic response to ramp stretch was elicited at all stretch velocities. There was no evidence for phasic responses to rapid stretch in reserpine-induced rigidity. The amplitude of the myomechanogram was thus found to be independent of the ramp stretch velocity. Subsequent injection of apomorphine abolished the increased stretch response. It is demonstrated that changes in muscle tone could be followed during drug treatment and that the method can be used in investigations of the pathophysiological mechanisms behind the disorders of muscle tone.

Physiological mechanisms and movement analysis in Parkinson's disease.

We present new ideas about motor control in the human central nervous system and about pathophysiological mechanisms of Parkinsons disease, and we describe the Posturo-Locomotion-Manual (PLM) method, which is a new technique utilizing optoelectronic camera recording for objective, fully quantitative, and standardized assessment of human motor performance. In the PLM test, recordings of body movements are made during a simple motor task, where the subject repeatedly moves a small object from its starting position on the floor to a shelf located at chin height a few steps forward. The duration of the postural (raising up), locomotor and the goal-directed manual phase of the forward directed body movement is automatically calculated by a small computer as well as the degree of coordination (simultaneity) of these phases. The technique has high resolution and has been used for clinical assessment of motor performance, drug testing, and so on, in neurological and geriatric practice.